International research consortium aims to build a reproducible single-cell sequencing workflow to capture tumour drug persistence

A  new  international  consortium  of  academic  and  industrial leaders in the field of cancer research is pleased to announce the launch of “PERSIST-SEQ”. This collaborative research program aims to provide the cancer research community with a new gold standard workflow for single-cell sequencing by developing and validating best practices as well as generating and analysing high-quality data. The  project  aims  to  empower  the  scientific  community  to  unravel  drug  resistance  and  develop  smarter therapeutic  strategies  to  better  treat  cancer  and prevent  resistance.  PERSIST-SEQ  is  a  five-year  public-private partnership, funded by the Innovative Medicines Initiative (IMI), and led by the Oncode Institute and
AstraZeneca.

Cancer takes 9.6 million lives each year, 90% of which result from untreatable cancer relapse occurring after initially effective treatment. Therapeutic resistance is one of the primary causes of cancer death and is clinically difficult to predict, prevent or treat. Although resistance has been studied extensively in the last decades, there is no comprehensive understanding of its underlying mechanisms, nor how they differ between cancer types or therapies. A better understanding of these mechanisms can contribute to better patient stratification, the development of effective drug strategies targeting the resistance mechanisms as well as improved cancer treatment strategies. Moreover, resistance is a major industrial challenge since it causes failure in the drug discovery and development process. Therapeutic resistance is largely unpredictable and difficult to model. Therefore, better tools are needed to identify or predict resistance mechanisms. These tools would, in turn, decrease the costs and risks associated with cancer drug development significantly.

“Drug resistance in cancer is one of the greatest causes of mortality and despite increasing success with targeted therapies in the clinic, how cancer cells survive drug treatment is still not well understood. We are excited to co-lead this European industry-academic partnership, using state-of-the-art single-cell sequencing to characterise 5 million single cells over 5 years to understand and overcome drug resistance.” - Ultan McDermott (AstraZeneca), industrial co-lead of PERSIST-SEQ.

Current  experimental  approaches  fail  to  study  residual  disease,  the  major  cause  of  cancer  relapse,  and therapeutic  resistance  in  clinically  meaningful  ways.  In  the  last  years  novel  methods  in  single-cell  sequencing have  seen  significant  advancements.  Such  techniques  combined  with  advanced  cancer  modelling  approaches can shed light on the intricate processes underlying therapeutic resistance and residual disease. Understanding the  mechanisms  of  cancer  resistance  is  crucial  to  enable  its  mitigation  and  requires  a  coordinated  effort.  To address these challenges, PERSIST-SEQ has formed a coalition of field-leading researchers and medical oncologists  on  cancer  resistance  who  will  leverage  their  ingenious  cancer  modelling  approaches  and  cutting-edge  techniques  to  perform  the  sequencing  of  single  tumour  cells.  PERSIST-SEQ  will  refine  and  standardise  a broadly  applicable  workflow  for  single-cell  sequencing  in  order  to  improve  the  understanding  of  therapeutic resistance in cancer and develop targeted prevention and mitigation techniques.

“I am very excited to be part of this consortium. Not only because of the importance of understanding tumour drug resistance, but also because we will perform this project in close collaboration with industrial partners. I am sure we will learn a lot from each other.” – Prof. Alexander van Oudenaarden (Hubrecht Institute), Principal Investigator of PERSIST-SEQ.

"The Colorectal Cancer Laboratory at IRB Barcelona has generated state of the art models of advanced cancer that mimic the disease in humans. These experimental models will allow the identification and characterization of cancer cell populations that persist after therapy and regenerate the tumor leading to disease relapse. We will investigate this problem through single-cell sequencing within the PERSIST-SEQ consortium. We are delighted to be part of such a powerful international frontier research project that will no doubt generate groundbreaking knowledge with an impact on oncological patient's lives" - Dr. Eduard Batlle (IRB Barcelona) states.

About the PERSIST-SEQ consortium

The ultimate goal of the PERSIST-SEQ consortium is to improve the understanding of therapeutic resistance in cancer and create effective strategies to improve cancer treatment and prevent drug  resistance. As a result of this effort, the project anticipates a significant step forward for the cancer community and its understanding of tumour plasticity. This can change the way scientists and clinicians view cancer and its related drug developments.  In order to achieve this goal, PERSIST-SEQ will develop a standardized  approach to single-cell sequencing workflows for the investigation of cells pre-treatment.  Uniquely, all experiments and pre-processing of  data  will  be  done  at  Single  Cell  Discoveries.  This  will  ensure  standardisation  and  continuity  of  both experimental  and  bioinformatics  workflows  throughout  the  project.  Importantly,  PERSIST-SEQ  will  employ  an open access model to build and sustain its benchmarking procedures and centralized European data infrastructure. This model reduces duplication of effort, thereby promoting collaboration across disciplines and ensuring  efficient  adoption  of  state-of-the-art  single  cell  technologies.  By  presenting  an  approach  which  is replicable,  the  PERSIST-SEQ  consortium  will  facilitate  a  further  investigation  of  unaddressed  tumours  and therapies. Therefore, the real impact of the project will stem from the growth of innovation capacity associated with the use of this approach across academic and industrial centres around the world.

PERSIST-SEQ is a public-private partnership funded by the IMI, with representation from academic institutions, small- and medium-sized enterprises, public organisations and pharmaceutical companies. The partners involved  in  the  project  are  Oncode  Institute,  Hubrecht  Institute,  Netherlands  Cancer  Institute,  Single  Cell Discoveries, Lygature, Wellcome Sanger Institute, Fondazione del Piemonte per l’Oncologia, Hubrecht Organoid Technology, Institute for Research in Biomedicine (IRB Barcelona), Vall d’Hebron Institute of Oncology, Xenopat, AstraZeneca, Merck KGaA, Darmstadt, Germany, Bayer, Transgene, Charles River.

Acknowledgement of support
PERSIST-SEQ  receives  funding  from  the  Innovative  Medicines  Initiative  2  Joint  Undertaking  under  grant
agreement No. 101007937. This Joint Undertaking receives support from the European Union’s Horizon 2020
research and innovation programme and EFPIA. See www.imi.europa.eu for more details.